Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes.

Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levels among Hp 1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.

Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes.

OBJECTIVE: We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles. RESULTS: HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050). CONCLUSIONS: The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.

Clinical and radiological features of Mycobacterium kansasii and other NTM infections.

BACKGROUND: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically. METHODS: The sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated. RESULTS: In the M. kansasii group, n = 27 (42%) were native-born Israelis compared to 9.4% (n = 3) of all other NTM groups (p = 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p = 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p = 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group. CONCLUSION: Major differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications.

Clinical and radiological features of Mycobacterium kansasii infection and Mycobacterium simiae infection.

This retrospective study sought to systematically identify clinical and radiological features of Mycobacterium kansasii and Mycobacterium simiae infections. The sample included consecutive patients with a culture-positive diagnosis of M. simiae infection (n=102) or M. kansasii infection (n=62) derived from the databases of the Laboratory of Microbiology of a tertiary medical centre and two outpatient tuberculosis centres. Data on patient background and clinical features were collected, and chest radiographs were analysed. Sixty percent of the M. kansasii group were native born compared to 18% of the M. simiae group (p=0.0001). M. simiae infection was associated with a higher rate of co-morbid disease, including diabetes mellitus, heart disease, and malignancy. A similar rate of lung disease was found in both groups. Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations, and M. simiae infection with more pulmonary infiltrates. Patients with M. simiae infection had a higher likelihood of middle and lower lobe disease whereas patients with M. kansasii infection had more upper lobe disease (p=0.001). Pleural effusions and lymphadenopathy were found only in the presence of M. simiae infection. We concluded that there are major differences in the epidemiologic features of M. kansasii and M. simiae infection which have important diagnostic and therapeutic implications.

Pulmonary Mycobacterium kansasii infection in Israel, 1999-2004: clinical features, drug susceptibility, and outcome.

BACKGROUND: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in world. However, little is known about its background characteristics or drug sensitivity in nonendemic areas. DESIGN: We assessed the clinical features, radiologic findings, and drug sensitivity associated with M kansasii infection in Israel. METHODS: Patients with a culture-positive diagnosis of M kansasii infection between April 1999 and April 2004 were identified from a clinic database of tuberculosis centers. Mycobacterial cultures were performed with standard methods. Data on patient background and clinical features were collected from the medical files. RESULTS: Mean age (+/- SD) of the 56 patients was 58 +/- 18 years, and 64% were men; 59% had associated lung disease. Fifteen percent were receiving immunosuppressive medications. None had HIV infection. Systemic comorbid diseases were noted in 27%. The most common clinical presentations were chest pain, cough, hemoptysis, fever, and night sweats. Cavitation was noted only in 54%. Older patients had more noncavitary disease than younger patients (p = 0.01, r = 0.35). Lower-lobe predominance was very rare (4%). None of the patients presented with pleural effusion or lymphadenopathy. Only seven patients (11%) underwent bronchoscopy for diagnosis. M kansasii isolates showed the highest sensitivity to rifampin, ethambutol, clarithromycin, and ofloxacin, and the highest resistance to ciprofloxacin and capreomycin. The mean duration of treatment was 21 +/- 7.2 months. There were no disease-related deaths. CONCLUSIONS: M kansasii disease in Israel has no association with HIV, more systemic comorbid diseases and associated lung disease, and fewer cavitations. Following appropriate treatment, patients with M kansasii disease have an excellent prognosis.